Changes In Hepatobiliary Function Research Articles

ACE Question

Article| December 2022 ACE Question ASA Monitor December 2022, Vol. 86, 11. https://doi.org/10.1097/01.ASM.0000904212.79262.98 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation ACE Question. ASA Monitor 2022; 86:11 doi: https://doi.org/10.1097/01.ASM.0000904212.79262.98 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: anesthesiology continuing education (ace) Which of the following physiological factors related to hepatobiliary function is MOST likely to increase during pregnancy? Physiological changes during pregnancy significantly impact the well-being of both mother and baby and are important to recognize for optimal anesthetic management. There are several relevant changes in hepatobiliary function that occur during pregnancy. Although cardiac output and blood flow to several organs (e.g., uterus, kidneys) increase significantly during pregnancy, hepatic blood flow does not change significantly. Most of the liver enzymes, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), remain within normal range. However, serum alkaline phosphatase more than doubles due to placental secretion of this enzyme. Pregnancy is associated with an increased frequency of gallstone disease. Acute appendicitis and acute cholecystitis are the most common diseases requiring surgery during pregnancy. Several factors, including biliary stasis and changes in bile composition, are implicated in creating a lithogenic environment for this higher frequency... You do not currently have access to this content.

The Hepatobiliary System: An Overview of Normal Function and Diagnostic Testing in Pregnancy.

Pregnancy is associated with physiological adaptions that affect every organ system. Changes in liver function in pregnancy have important effects on nutrient metabolism, protein synthesis, and the biotransformation of substances in preparation for excretion. A clear understanding of the anatomic and functional changes of the hepatobiliary system is necessary for the diagnosis and evaluation of disease, as well as understanding how these changes predispose women to pregnancy-specific hepatic conditions. In this review, the effect of gestational changes in hepatobiliary function on laboratory tests and the role of diagnostic imaging of the liver and gallbladder in pregnancy will be discussed.

Bile constituents in hibernating golden-mantled ground squirrels (Spermophilus lateralis)

BackgroundGolden-mantled ground squirrels (S. lateralis) are anorexic during the winter and survive by exploiting hibernation to reduce energetic demands. The liver normally plays a critical role in fueling and regulating metabolism and one might expect significant changes in hepatobiliary function with hibernation. We analyzed bile collected from animals in summer, animals in winter that were either torpid, active between bouts of torpor, or which failed to enter hibernation in order to characterize the effects of hibernation on hepatobiliary function per se.ResultsSurprisingly, hibernator bile did not differ from summer squirrel bile in key characteristics including [bile acids], [cholesterol], [free fatty acids], [lecithin], and osmolality. One major distinction between summer and winter squirrels was that winter squirrels experience >5 fold increases in [bilirubin]. Such an increase may have significant physiological consequences that could aid in survivorship of torpor. Animals that failed to hibernate, despite being anorexic, were very similar to summer squirrels in all measured parameters except they had lower bile acid and lecithin concentrations.ConclusionThe data indicate that despite extended anorexia, differences in metabolic fuel privation, and bouts of reduced body temperatures, hibernators normally do not experience broad changes in hepatobiliary function.

Guidelines for imaging focal lesions in liver cirrhosis

Imaging cirrhotic patients for early detection of hepatocellular carcinoma remains a challenging issue despite many technological advances. In fact, nonmalignant hepatocellular lesions, such as regenerative or dysplastic nodules, may mimic a small tumor. Imaging protocols are aimed at showing the different vascular supply to the lesion. It is accepted that dynamic contrast-enhanced imaging techniques, including contrast ultrasound, multidetector computed tomography and magnetic resonance imaging, can establish the diagnosis of hepatocellular carcinoma in nodular lesions larger than 1 cm showing arterial hypervascularization with venous washout. Magnetic resonance imaging in combination with liver-specific contrast agents, including hepatocyte-targeted and reticuloendothelial system-targeted agents, may be useful to clarify questionable cases, due to its ability to show changes in hepatobiliary function or Kuppfer cell content associated with malignancy. However, even optimized imaging techniques remain relatively insensitive for the detection of tiny satellite nodules associated with the main tumor.

Serum bile acids as a sensitive biological marker for evaluating hepatic effects of organic solvents

Serum bile acids (SBAs) are suggested as a potentially sensitive and specific indicator of liver function which, accordingly, could provide an early indication of hepatobiliary dysfunction. This offers advantages over more traditional parameters of liver integrity/function. Recent studies have shown that occupational exposure to low levels of halogenated aliphatic or non-halogenated aromatic solvents is associated with significant increases in SBA levels. As this has often been evident in the absence of any effect on conventional parameters of hepatobiliary integrity/function, elevated SBA levels may well be regarded as a sensitive biological marker of exposure/effect of these compounds. In addition, it may be considered that they provide an early indicator of solvent-induced changes in hepatobiliary function. Extensive studies with experimental animals have also provided supporting evidence for these observations in solvent-exposed individuals. Investigations of the mechanisms at cellular and subcellular levels by which these increases occur have suggested that these effects are likely to be the result of selective, dose-related and reversible inhibition of bile acid uptake at the sinusoidal domain of the hepatocyte plasma membrane. Increased concentrations of SBA under low levels of exposure to different solvents have been demonstrated to be a short-lived and reversible effect which is not accompanied by any other evidence of liver damage. Therefore, it could be assumed that it is unlikely that there would be pathological sequelae to these effects, although the longer term ramifications of such effects have not been thoroughly investigated. Nevertheless, the available evidence indicates that investigation of SBA in solvent-exposed workers could provide useful indications of exposure and effect.

Subchronic Toxicity Studies of Sucrose Acetate Isobutyrate (SAIB) in the Ratand Dog

Preliminary short-term toxicity studies of sucrose acetate isobutyrate (SAIB) in the dog demonstrated that addition of this additive to the diet was associated with an increase in liver size and elevated serum alkaline phosphatase activity with no evidence of pathological change by light microscopy. To determine the basis for these changes, a 12-week oral toxicity study of SAIB was conducted in the dog and a similar study was performed in the rat. SAIB was fed in the diet to groups of six beagle dogs of each sex at 0, 0.5, 1.0, 2.0 and 4.0%. SAIB was also fed to groups of 40 Sprague--Dawley rats of each sex at levels of 0, 2.5, 5.0 and 10.0%. In the rat study, in addition to routine toxicology parameters, hepatic microsomal enzyme induction was determined using a zoxazolamine hypnotic test, urinary ascorbic acid excretion and determination of hepatic carboxylesterase activity. Sodium phenobarbital was fed to groups of 20 rats of each sex at a dose of 100mg/kg body weight/day by gavage as a positive control for hepatic microsomal enzyme induction. In the dog study, routine toxicological tests were supplemented by tests for bromsulfophthalein (BSP) retention, histochemical staining of liver sections for glycogen, phosphorylase, succinate dehydrogenase, and acid and alkaline phosphatases. Levels of liver lipid, protein, glycogen and carboxylesterase activity were also determined. Electron microscopic examinations were made on liver sections from the dog study at the end of the 12-week SAIB feeding period and after a 2-week withdrawal period. Administration of SAIB to rats did not reveal evidence of any effect on hepatobiliary function, and there was no indication of microsomal enzyme induction. Body weight gain of male rats fed SAIB was decreased, probably as the result of decreased palatability of the diet; SAIB did not affect body weight gain in females. The changes observed in the dogs fed SAIB included increased serum alkaline phosphatase activity with no change in serum alanine aminotransferase, aspartate aminotransferase or lactic dehydrogenase activity and no change in serum electrolyte, serum protein, glucose or bilirubin levels. No haematological changes were observed. BSP retention was observed at all SAIB dose levels. There were no SAIB-related pathological changes in any organ when examined by light microscopy. Examination by electron microscope revealed dilatation of bile canaliculi and an increase in smooth endoplasmic reticulum compared with controls. Histochemical studies also indicated increased enzyme activity of the bile canaliculi. The electron-mocroscope-revealed changes were completely reversed during a 2-week treatment withdrawal period. The dog study did not establish a no-effect level for changes in hepatobiliary function induced by feeding SAIB.

Assessment of hepatobiliary function in vivo and ex vivo in the rat

Many xenobiotics cause hepatobiliary toxicity and cholestasis in the rat. Initial assessment of hepatobiliary damage in rats can be accomplished by measuring serum concentrations of bile acids and bilirubin, serum activities of liver-associated enzymes such as 5'-nucleotidase, alkaline phosphatase, γ-glutamyltranspeptidase, and plasma clearances of dyes [e.g., bromosulfophthalein (BSP)] excreted primarily through the bile. More detailed evaluation of hepatobiliary disturbances involves cannulation of the bile duct of anesthetized rats and subsequent measurement of rates of bile flow, bile acid excretion, and bile composition. Canalicular bile flow can be estimated from clearances of nonmetabolized sugars (i.e., erythritol) which enter bile via paracellular transport. Tight junction permeability also can be assessed by either biliary excretion of such a marker as horseradish peroxidase or sucrose following portal vein infusion or via retrograde biliary infusion. Subsequent morphologic evaluation of the liver provides information on damage to cells which may contribute to hepatobiliary dysfunction (i.e., bile duct obstruction). Isolated perfused livers offer the ability to measure all of the abovementioned parameters as well as to make a more accurate determination of the effects of xenobiotics on bile acid-dependent and -independent bile flow. A good example of the advantage of combining techniques as well as following complete time courses of changes in hepatobiliary function is provided by using studies of α-naphthylisothiocyanate-induced hepatotoxicity.

Temporal Relationship of Changes in Hepatobiliary Function and Morphology in Rats Following α-Naphthylisothiocyanate (ANIT) Administration

These studies were designed to evaluate ANIT-induced changes in both hepatobiliary function and morphology during the onset, progression, and recovery of ANIT-induced cholestasis. A single oral dose of 150 mg/kg of ANIT or vehicle was administered by gavage to male Sprague-Dawley rats and hepatobiliary structure and function were evaluated 16, 24, 48, 72, and 168 hr later. Increased hepatocellular tight junction permeability, increased serum bile acids, and decreased bile acid excretion were observed 16 hr after ANIT administration. At 24 hr, bile flow was decreased in ANIT-treated rats, an effect accompanied by increased tight junction permeability, decreased bile acid excretion, and decreased erythritol clearance (estimate of canalicular flow). In addition, scattered small loci of hepatocellular necrosis accompanied by an inflammatory cell response were observed in ANIT-treated rats at this time, with no microscopic evidence of bile duct obstruction (BDO). These data suggest that the onset of ANIT-induced cholestasis was associated with hepatocanalicular changes and not BDO. In contrast, at 48 and 72 hr after ANIT treatment, cholestasis was more profound and was accompanied by mild hepatocellular necrosis and widespread BDO. Hepatocyte tight junction permeability in ANIT-treated rats was not different from controls at 72 hr. These data suggest that the pathogenesis of ANIT-induced cholestasis is biphasic; the onset of cholestasis appears to be associated with changes in hepatocanalicular function and increased tight junction permeability whereas the later and more profound phase of cholestasis appears to be related to a combination of BDO and hepatocellular dysfunction. The time course of biochemical and morphologic changes following ANIT treatment further suggests that the pathophysiologic changes during the onset or initiation phase of cholestasis differ from those involved in the later and more profound phase of ANIT-induced cholestasis.

Early hepatobiliary dysfunction during total parenteral nutrition: An experimental study

The etiology and pathophysiology of the liver disease associated with total parenteral nutrition (TPN) are unknown. In this study, we have attempted to define the early changes in hepatobiliary function during TPN in young rabbits nourished totally by the intravenous route for 3, 5, and 15 days, with age-matched rabbits on lab chow serving as controls. A decrease in basal bile flow along with elevations of serum bile acids and cholesterol was seen. The capacity for biliary secretion of sulfobromophthalein and of ursodeoxycholic acid was measured at the end of each diet regimen. Early impairment of biliary sulfobromophthalein (BSP) secretion was seen after 5 days of TPN, with no further deterioration after 15 days. Maximal bile acid secretory rate and bile flow, in response to the ursodeoxycholic acid load, were decreased after 15 days of TPN. Furthermore, after 15 days of TPN, both the volume of gallbladder bile and its bile acid content increased. The combined effects of the enteral fast and the intravenous administration of all nutrients were bile acid sequestration in an adynamic gallbladder with interruption of the enterohepatic circulation. In the parenterally fed rabbit, we have demonstrated bile secretory failure and gallbladder sludge, the two common complications of clinical TPN. These may be the early events that subsequently lead to cholestasis and liver damage in neonates maintained on prolonged TPN.

GALLSTONE DISEASE AND PANCREATITIS IN PREGNANCY

Controversy exists over whether pregnancy is a risk factor for gallstone formation; however, changes in hepatobiliary function do occur during pregnancy to create a lithogenic environment; these changes include gallbladder stasis and secretion of bile with increased amounts of cholesterol and decreased amounts of chenodeoxycholic acid. In women with existing gallstones, pregnancy may bring out symptoms, including pain and even acute cholecystitis. This may be more common during the postpartum period than during pregnancy itself; however, the overall occurrence of symptomatic biliary disease in association with pregnancy is low. The effects of pregnancy, if any, on pancreatic exocrine function are undefined. Acute pancreatitis can occur during pregnancy but does not appear to do so with either increased or, alternatively, decreased frequency. The concept of pancreatitis caused by pregnancy per se is not valid, although in susceptible women with lipid disorders, hypertriglyceridemia can occur and serve as an etiologic factor. Gallstones are a common cause of pancreatitis, but in contrast to nonpregnant women, alcohol is unusual as a cause. Although the presentation of both acute cholecystitis and acute pancreatitis may be similar to that in the nonpregnant state, the differential diagnosis of both these disorders is expanded because of unique pregnancy-related conditions and the shift of abdominal viscera by the enlarging uterus. The diagnosis is clinical and supported with conventional laboratory studies and ultrasound; management is supportive and in most patients successful. Cholecystectomy is seldom necessary during pregnancy, either for acute cholecystitis or gallstone pancreatitis, but can be safely performed if necessary after the first trimester. Endoscopic papillotomy and stone removal for choledocholithiasis are possible during pregnancy and may be the treatment of choice for this unusual condition. Specific enteral or parenteral nutrition may be necessary in women with pancreatitis associated with hypertriglyceridemia.

Laboratory Evaluation of Liver Disease

With respect to liver disease, the primary function of the laboratory is to identify its presence. Tests are not available that permit a specific diagnosis and an accurate prognosis. Several tests should be present in a minimum data base that can help identify hepatobiliary disease. They are ALT, SAP, total serum bilirubin, urine bilirubin, cholesterol, albumin, BUN, glucose, red cell morphology, and urine sediment. It is sometimes possible to tentatively identify whether a disease is primarily hepatocellular or biliary from the pattern of changes that occur in these tests. In addition, an estimate of the severity is sometimes possible when abnormal values are extreme. The keys are to avoid overinterpretation, use serial evaluations, and rely on a liver biopsy when definitive answers are needed. If liver disease is suspected but there are only marginal changes in the routine tests, the more sensitive tests of function, BSP retention and ammonia tolerance, are warranted. In the future, as more knowledge is gained about the responses of ARG, GGT, and ICG retention to naturally occurring diseases, these tests may join or replace some of those currently used. Also, as the ability to accurately and economically measure the various bile acids improves, a sensitive, yet noninvasive, method to detect and define modest changes in hepatobiliary function may result.

Effect of Pregnancy on Bile Flow and Biliary Lipids in the Hamster

The administration of estrogens and oral contraceptive steroids containing estrogen and a progestogen affects biliary lipids, bile acids, and bile flow in a number of animal species. The physiologic relevance of these observations has been examined in the hamster by studying hepatobiliary function in pregnancy, a state characterized by high levels of estrogens and progesterone. The rate of bile flow and the excretion of biliary lipids were studied on the 9th and 14th days of pregnancy and compared with those of nonpregnant females and males of similar ages. The authors measured the concentration, composition, and secretion of bile acids, phospholipids, and cholesterol in hepatic bile. There were no differences in these measurements between males and nonpregnant females. In pregnant females, the following changes were observed: (a) a progressive fall in bile flow, which in late pregnancy (14th day) was decreased 62%; the decrease in bile flow (67%) was principally in the bile acid-independent fraction; (b) reduced secretion of total bile acids due to decreased cholic acid secretion; the decreased output of bile acid, especially cholic acid, may reflect a reduced pool size during pregnancy; (c) increased concentration of biliary lipids but no significant change in the lithogenic index of bile; and (d) the appearance of β-muricholic and hydodeoxycholic acids in the bile. In addition, (Na+K+)ATPase activity was reduced but (Mg++)ATPase activity was not altered in liver homogenates of 14-day pregnant animals. These effects of pregnancy—decreased bile acid-independent bile flow, decreased hepatic (Na+K+)ATPase activity, and decreased cholic acid secretion—are similar to those produced by estrogen administration in hamsters and rats. The findings stress the importance of changes in hepatobiliary function produced by female sex hormones in an important physiologic state.